ETD

• biliary tract cancers
• molecular profiling
• prognosis
• targetable alterations

Targeted treatments have deeply changed the treatment algorithm for advanced biliary tract cancers (BTCs) harbouring genomic alterations; however, to less is known about the potential role of multiple targetable alterations.
This is an observational, multicenter and international study enrolling 686 patients with BTCs diagnosed between 2015 and 2024. Current analyses are focused on the incidence of multiple targetable alterations and their impact on outcomes.
Fifty patients (7.3%) harbored multiple targetable alterations, without a clearly dominant pair in our cohort. They were more likely to have intrahepatic cholangiocarcinoma than patients with no targetable alterations. Of 555 patients diagnosed with advanced diseases, those with multiple targetable alterations had better overall survival (OS) and progression-free survival (PFS) than those without targetable alterations, although no differences were seen in response rate according to the number of targetable alterations. Of 82 patients with at least one targetable alterations who received tailored treatment, only 14 had multiple targetable alterations. We found no difference in OS and PFS between patients with single and multiple targetable alterations.
Despite a broader knowledge of genomic alterations and availability of targeted treatment in advanced BTCs, the role of co-occurring targetable alterations remains poorly understood. Our results demonstrate that multiple targetable alterations could confer better prognosis in advanced BTCs patients and could not act as a outcomes modifier in patients treated both with first-line systemic chemotherapy and targeted treatment. Further investigations into this cohort of patients are warranted.